Pulmonary reperfusion injury: evidence for oxygen-derived free radical mediated damage and effects of different free radical scavengers.
Blood granulocyte-mediated reactions involving generation of oxygen-derived free radicals have recently been shown to be capable of causing injury to the lungs. These findings suggest a similar mechanism also to be involved in the development of pulmonary ischemia/reperfusion injury. In the present study, therefore, the effects of three oxygen-derived free radical scavengers, superoxide dismutase (SOD; 1 mg/kg), catalase (20,000 IU/kg) and allopurinol (45 mg/kg), were evaluated during reperfusion in a rabbit model after 2 h normothermic ischemia of the lung. During reperfusion, ischemic lungs were found to have an elevated pulmonary vascular resistance, increased total and extravascular lung water content, and decreased arterial oxygen tension (PaO2) compared to control animals. SOD and catalase, but not allopurinol, were able to reduce pulmonary injury by lowering the pulmonary vascular resistance, but could not prevent pulmonary damage as shown by total lung water (TLW) or PaO2. It is concluded that oxygen-derived free radicals such as hydrogen peroxide and the superoxide anion may play an important role in precipitating pulmonary injury after ischemia. The failure of xanthine oxidase inhibition (allopurinol) to exert protective effects may suggest that oxygen-derived free radical generation following pulmonary ischemia occurs predominantly via leukocyte-mediated reactions.
Jurmann
M J
MJ
Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, FRG.
Dammenhayn
L
L
Schaefers
H J
HJ
Haverich
A
A
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002374:Catalase / Q000494:pharmacology; D015633:Extravascular Lung Water / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers; D005609:Free Radicals; D006801:Humans; D008168:Lung / Q000098:blood supply*; D010100:Oxygen / Q000097:blood; D011652:Pulmonary Circulation / Q000187:drug effects; D011817:Rabbits; D015427:Reperfusion Injury / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D016166:Free Radical Scavengers; D005609:Free Radicals; D000493:Allopurinol; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen